Opioid dependence is a serious public health problem, particularly with the dramatic rise in prescription opioid (PO) abuse, but long-term opioid agonist maintenance with methadone or buprenorphine (BUP) may not be optimal for many PO abusers. Yet current opioid detoxification strategies are limited by high relapse rates and/or lack of efficacy in relieving subjective symptoms. In addition, antagonist maintenance with naltrexone (NTX), which may be an optimal longer-term strategy for this population, requires prior opioid detoxification and has been associated with relatively poor outcomes in heroin abusers. This application takes a novel, broad approach to address the problem of PO dependence by determining the 1) utility of adjunct gabapentin (GBP) during outpatient BUP detoxification to improve initial outcomes and 2) feasibility of transitioning PO-dependent patients to depot NTX following detoxification, which may improve longer-term outcomes. GBP, an N-type calcium channel blocker with low abuse potential, potentiates opioid analgesia, decreases both postoperative morphine consumption and movement-related pain, and reverses tolerance to the antinociceptive effects of morphine. GBP is also well tolerated and effective in reducing craving and illicit opioid use in pilot detoxification trials. We propose to assess the efficacy and tolerability of adjunct GBP during BUP-assisted detoxification and the feasibility of subsequent transition to depot NTX therapy in PO-dependent participants. This 8-week, randomized, placebo-controlled clinical trial will determine the potential utility of adjunct GBP i 150 PO- dependent individuals undergoing outpatient BUP detoxification and whether transition to short-term depot NTX therapy is feasible. Our three specific aims are to determine (1) the efficacy and tolerability of GBP to reduce craving and illicit use of opioids in PO-dependent individuals undergoing outpatient BUP detoxification; (2) acceptability and feasibility of transitin to, and short-term maintenance on, depot NTX following detoxification; and (3) prognosticators of completion of the BUP taper, successful induction onto depot NTX, symptomatology, and longer-term outcomes. Currently, the only FDA-approved medications for the treatment of opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse liability, and NTX, which can produce low levels of withdrawal-like symptoms, especially early in treatment. Our findings, if positive, will support further development of GBP as an adjunct medication as well as provide an integrated, seamless approach to outpatient PO-dependence treatment. Ultimately, this work could impact the addiction field by providing both procedural and pharmacological tools for treating PO dependence that significantly improve outpatient detoxification outcomes and markedly enhance access and transition to NTX therapy. This would shift clinical practice, establishing an effective adjunct regimen for BUP detoxification and an integrated approach f or transition to NTX therapy. GBP may also be clinically useful for other situations where opioid withdrawal is a concern.